Aim: This study aimed to compare the effects of opioid versus non-opioid analgesics in post-surgical pain management, specifically evaluating the degree of pain relief and the incidence of side effects in patients undergoing minor to moderately invasive surgeries. Material and Methods: A total of 100 patients who underwent elective surgeries were randomly selected from a hospital setting. Inclusion criteria required patients to be aged 18–65, undergoing minor to moderately invasive procedures, and without contraindications to either opioid or non-opioid medications. Exclusion criteria included a history of opioid use disorder, chronic pain conditions, allergies to study medications, and impaired renal or hepatic function. Patients were randomly assigned to one of two groups: the opioid group (receiving morphine or hydromorphone) and the non-opioid group (receiving a combination of NSAIDs and acetaminophen). Pain intensity was measured using the Visual Analog Scale (VAS) at regular intervals post-surgery, and adverse effects were documented. Results: The demographic characteristics of both groups were similar. Pain intensity at 1 hour post-surgery was significantly higher in the opioid group (6.2 ± 1.8) compared to the non-opioid group (5.1 ± 2.1), with a p-value of 0.04. However, by 4 hours post-surgery, the difference in pain intensity between groups became less pronounced (p = 0.08). By 8, 12, and 24 hours, no significant differences were observed in pain intensity (p-values 0.12, 0.35, and 0.27, respectively). The incidence of side effects was significantly higher in the opioid group, with nausea (64% vs. 28%, p = 0.02), dizziness (56% vs. 20%, p = 0.03), and gastrointestinal issues (44% vs. 12%, p = 0.01), particularly constipation (36% vs. 0%, p = 0.02). Headaches were more frequent in the non-opioid group (36% vs. 16%, p = 0.05). Multiple regression analysis revealed that opioid use was associated with a higher VAS score (p = 0.001) and older age was a significant predictor of higher pain intensity (p = 0.003). Conclusion: Opioids provided superior immediate pain relief compared to non-opioid analgesics but showed diminishing effectiveness beyond the first few hours post-surgery. Additionally, opioids were associated with a higher incidence of adverse effects, particularly gastrointestinal issues. These findings suggest that non-opioid analgesics may offer a safer long-term alternative for post-surgical pain management, particularly for minimizing side effects.